How effective early pharmacological intervention is in preventing pancreatitis (PEP) after endoscopic retrograde cholangiopancreatography (ERCP) has been controversial. Dr. Kubiliun et al. from Texas Southwestern University conducted a systematic review of the safety and efficacy of pharmacological prophylaxis for PEP, suggesting that rectally applied NSAIDs may be appropriate for the prevention of PEP, especially in high-risk patients, as published in the recent CLIN GASTROENTEROL H The study system was searched for all randomized controlled trial studies (RCTs) and meta-analysis literature on drug prophylaxis for PEP up to February 2014. After browsing 851 publications, 85 RCT studies and 28 meta-analyses were screened for eligibility, and a total of 28,857 patients were randomly assigned to 28 different drug prophylaxis modalities and their placebo groups. The different studies were classified and delineated for study characteristics, clinical outcomes and risk of error extraction information, (1) drugs suitable for clinical application, (2) drugs that have been confirmed in validated randomized controlled trials with promising and high priority levels, (3) drugs that still need further confirmation in large scale exploratory RCT clinical trials, and (4) drugs with low likelihood of effectiveness or inadequate data proof. Clinical and research recommendations were developed for various drug prevention consultations after combining study classification results and important factors, such as the degree of patient benefit, safety, utility, and cost. A systematic review found that among the first class of drugs appropriate for clinical use, rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) reduced the incidence of PEP by 64% (relative risk 0.36, 912 patients) without increasing the risk of adverse events (the trial NSAIDs were 100 mg indomethacin or diclofenac). In contrast, patients did not benefit from oral, intramuscular, or intravenous administration of NSAIDs, and the exact mechanism for this is not yet clear. The second group of promising drugs, including sublingual nitroglycerin, growth inhibitor pills, and nafamostat, have been shown in RCTs and meta-analyses to reduce the risk of PEP to varying degrees, and have been shown to be more effective when combined with rectal indomethacin than when combined with rectal indomethacin alone. Dr. Kubiliun et al. mentioned that sublingual nitroglycerin may be considered for the prevention of PEP in patients with allergy to NSAIDs and in patients who are unwilling or unable to receive pancreatic stents. The third category of pharmacological prophylaxis includes topical application of epinephrine (sprayed on the duodenal papilla), intravenous rehydration, gabexate, ustekin, glucagon, and antibiotics. Current trial data on these pharmacological prophylaxis methods are conflicting and still need to be further confirmed in large exploratory RCT clinical trials. The fourth category of drugs with low likelihood of effectiveness or inadequate data proof includes allopurinol, antioxidants, glucocorticoids, and octreotide, and the trial studies on these have mainly negative results and cannot be used for PEP prophylaxis. In summary of the results of the systematic review, rectal application of NSAIDs may be appropriate for the prevention of PEP, especially in high-risk patients, and the European Society of Gastrointestinal Endoscopy recommends that rectal administration of indomethacin or diclofenac may be used for the prevention of PEP in patients with ERCP, either preoperatively or immediately after surgery, with a class A recommendation. The preventive effect of other drugs on PEP needs to be confirmed by further studies, among which sublingual nitroglycerin and growth inhibitor pills should be considered as the highest priority for clinical trials, while the combination of drugs and the combination with pancreatic duct stents is expected to minimize the incidence of PEP, and these findings can guide the direction for future research and clinical decisions.